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Erschienen in: Journal of Natural Medicines 2/2017

24.12.2016 | Original Paper

Antidepressant-like effects of ginsenoside Rg3 in mice via activation of the hippocampal BDNF signaling cascade

verfasst von: Zhengchen You, Qi Yao, Jianhong Shen, Zhikai Gu, Hui Xu, Zhonghua Wu, Chuanjun Chen, Luozhu Li

Erschienen in: Journal of Natural Medicines | Ausgabe 2/2017

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Abstract

Current antidepressants are clinically effective only after several weeks of administration. Ginsenoside Rg3 is one component of ginsenosides, with a similar chemical structure to ginsenoside Rg1. Here, we investigated the antidepressant effects of Rg3 in mouse models of depression. The antidepressant actions of Rg3 were first examined in the forced swim test (FST) and tail suspension test (TST), and then assessed in the chronic social defeat stress (CSDS) model of depression. The changes in the hippocampal brain-derived neurotrophic factor (BDNF) signaling pathway after CSDS and Rg3 treatment were investigated. A tryptophan hydroxylase inhibitor and a BDNF signaling inhibitor were also used to determine the pharmacological mechanisms of Rg3. It was found that Rg3 produced antidepressant effects in the FST and TST without affecting locomotor activity. Rg3 also prevented the CSDS-induced depressive-like symptoms. Moreover, Rg3 fully restored the CSDS-induced decrease in the hippocampal BDNF signaling pathway, and use of the BDNF signaling inhibitor blocked the antidepressant effects of Rg3. In conclusion, ginsenoside Rg3 has antidepressant effects via promotion of the hippocampal BDNF signaling pathway.
Literatur
1.
Zurück zum Zitat Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S et al (1994) Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 51:8–19CrossRefPubMed Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S et al (1994) Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 51:8–19CrossRefPubMed
2.
Zurück zum Zitat Thase ME (2006) Preventing relapse and recurrence of depression: a brief review of therapeutic options. CNS Spectr 11:12–21CrossRefPubMed Thase ME (2006) Preventing relapse and recurrence of depression: a brief review of therapeutic options. CNS Spectr 11:12–21CrossRefPubMed
3.
Zurück zum Zitat McGrath PJ, Stewart JW, Fava M, Trivedi MH, Wisniewski SR, Nierenberg AA et al (2006) Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry 163:1531–1541 quiz 1666 CrossRefPubMed McGrath PJ, Stewart JW, Fava M, Trivedi MH, Wisniewski SR, Nierenberg AA et al (2006) Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry 163:1531–1541 quiz 1666 CrossRefPubMed
4.
Zurück zum Zitat Shaywitz AJ, Greenberg ME (1999) CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem 68:821–861CrossRefPubMed Shaywitz AJ, Greenberg ME (1999) CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem 68:821–861CrossRefPubMed
5.
Zurück zum Zitat Lim JY, Park SI, Oh JH, Kim SM, Jeong CH, Jun JA et al (2008) Brain-derived neurotrophic factor stimulates the neural differentiation of human umbilical cord blood-derived mesenchymal stem cells and survival of differentiated cells through MAPK/ERK and PI3K/Akt-dependent signaling pathways. J Neurosci Res 86:2168–2178CrossRefPubMed Lim JY, Park SI, Oh JH, Kim SM, Jeong CH, Jun JA et al (2008) Brain-derived neurotrophic factor stimulates the neural differentiation of human umbilical cord blood-derived mesenchymal stem cells and survival of differentiated cells through MAPK/ERK and PI3K/Akt-dependent signaling pathways. J Neurosci Res 86:2168–2178CrossRefPubMed
6.
Zurück zum Zitat Castren E, Kojima M (2016) Brain-derived neurotrophic factor in mood disorders and antidepressant treatments. Neurobiol Dis S0969–S9961(16):30169 Castren E, Kojima M (2016) Brain-derived neurotrophic factor in mood disorders and antidepressant treatments. Neurobiol Dis S0969–S9961(16):30169
7.
Zurück zum Zitat Monteleone P, Serritella C, Martiadis V, Maj M (2008) Decreased levels of serum brain-derived neurotrophic factor in both depressed and euthymic patients with unipolar depression and in euthymic patients with bipolar I and II disorders. Bipolar Disord 10:95–100CrossRefPubMed Monteleone P, Serritella C, Martiadis V, Maj M (2008) Decreased levels of serum brain-derived neurotrophic factor in both depressed and euthymic patients with unipolar depression and in euthymic patients with bipolar I and II disorders. Bipolar Disord 10:95–100CrossRefPubMed
8.
Zurück zum Zitat Duman RS (2004) Role of neurotrophic factors in the etiology and treatment of mood disorders. Neuromol Med 5:11–25CrossRef Duman RS (2004) Role of neurotrophic factors in the etiology and treatment of mood disorders. Neuromol Med 5:11–25CrossRef
9.
Zurück zum Zitat Duman RS, Voleti B (2012) Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents. Trends Neurosci 35:47–56CrossRefPubMedPubMedCentral Duman RS, Voleti B (2012) Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents. Trends Neurosci 35:47–56CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Blendy JA (2006) The role of CREB in depression and antidepressant treatment. Biol Psychiatry 59:1144–1150CrossRefPubMed Blendy JA (2006) The role of CREB in depression and antidepressant treatment. Biol Psychiatry 59:1144–1150CrossRefPubMed
14.
Zurück zum Zitat Lee YY, Park JS, Jung JS, Kim DH, Kim HS (2013) Anti-inflammatory effect of ginsenoside Rg5 in lipopolysaccharide-stimulated BV2 microglial cells. Int J Mol Sci 14:9820–9833CrossRefPubMedPubMedCentral Lee YY, Park JS, Jung JS, Kim DH, Kim HS (2013) Anti-inflammatory effect of ginsenoside Rg5 in lipopolysaccharide-stimulated BV2 microglial cells. Int J Mol Sci 14:9820–9833CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Zhang Y, Zhang Z, Wang H, Cai N, Zhou S, Zhao Y et al (2016) Neuroprotective effect of ginsenoside Rg1 prevents cognitive impairment induced by isoflurane anesthesia in aged rats via antioxidant, anti-inflammatory and anti-apoptotic effects mediated by the PI3 K/AKT/GSK-3beta pathway. Mol Med Rep 14:2778–2784PubMed Zhang Y, Zhang Z, Wang H, Cai N, Zhou S, Zhao Y et al (2016) Neuroprotective effect of ginsenoside Rg1 prevents cognitive impairment induced by isoflurane anesthesia in aged rats via antioxidant, anti-inflammatory and anti-apoptotic effects mediated by the PI3 K/AKT/GSK-3beta pathway. Mol Med Rep 14:2778–2784PubMed
16.
Zurück zum Zitat Chen J, Wang Q, Wu H, Liu K, Wu Y, Chang Y et al (2016) The ginsenoside metabolite compound K exerts its anti-inflammatory activity by downregulating memory B cell in adjuvant-induced arthritis. Pharm Biol 54:1280–1288CrossRefPubMed Chen J, Wang Q, Wu H, Liu K, Wu Y, Chang Y et al (2016) The ginsenoside metabolite compound K exerts its anti-inflammatory activity by downregulating memory B cell in adjuvant-induced arthritis. Pharm Biol 54:1280–1288CrossRefPubMed
17.
Zurück zum Zitat Dong X, Zheng L, Lu S, Yang Y (2015) Neuroprotective effects of pretreatment of ginsenoside Rb1 on severe cerebral ischemia-induced injuries in aged mice: involvement of anti-oxidant signaling. Geriatr Gerontol Int. doi:10.1111/ggi.12699 Dong X, Zheng L, Lu S, Yang Y (2015) Neuroprotective effects of pretreatment of ginsenoside Rb1 on severe cerebral ischemia-induced injuries in aged mice: involvement of anti-oxidant signaling. Geriatr Gerontol Int. doi:10.​1111/​ggi.​12699
18.
19.
Zurück zum Zitat Jiang B, Xiong Z, Yang J, Wang W, Wang Y, Hu ZL et al (2012) Antidepressant-like effects of ginsenoside Rg1 are due to activation of the BDNF signalling pathway and neurogenesis in the hippocampus. Br J Pharmacol 166:1872–1887CrossRefPubMedPubMedCentral Jiang B, Xiong Z, Yang J, Wang W, Wang Y, Hu ZL et al (2012) Antidepressant-like effects of ginsenoside Rg1 are due to activation of the BDNF signalling pathway and neurogenesis in the hippocampus. Br J Pharmacol 166:1872–1887CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Kim JH, Cho SY, Lee JH, Jeong SM, Yoon IS, Lee BH et al (2007) Neuroprotective effects of ginsenoside Rg3 against homocysteine-induced excitotoxicity in rat hippocampus. Brain Res 1136:190–199CrossRefPubMed Kim JH, Cho SY, Lee JH, Jeong SM, Yoon IS, Lee BH et al (2007) Neuroprotective effects of ginsenoside Rg3 against homocysteine-induced excitotoxicity in rat hippocampus. Brain Res 1136:190–199CrossRefPubMed
21.
Zurück zum Zitat Tian J, Fu F, Geng M, Jiang Y, Yang J, Jiang W et al (2005) Neuroprotective effect of 20(S)-ginsenoside Rg3 on cerebral ischemia in rats. Neurosci Lett 374:92–97CrossRefPubMed Tian J, Fu F, Geng M, Jiang Y, Yang J, Jiang W et al (2005) Neuroprotective effect of 20(S)-ginsenoside Rg3 on cerebral ischemia in rats. Neurosci Lett 374:92–97CrossRefPubMed
22.
Zurück zum Zitat Kim J, Shim J, Lee S, Cho WH, Hong E, Lee JH et al (2016) Rg3-enriched ginseng extract ameliorates scopolamine-induced learning deficits in mice. BMC Complement Altern Med 16:66CrossRefPubMedPubMedCentral Kim J, Shim J, Lee S, Cho WH, Hong E, Lee JH et al (2016) Rg3-enriched ginseng extract ameliorates scopolamine-induced learning deficits in mice. BMC Complement Altern Med 16:66CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Kim TW, Choi HJ, Kim NJ, Kim DH (2009) Anxiolytic-like effects of ginsenosides Rg3 and Rh2 from red ginseng in the elevated plus-maze model. Planta Med 75:836–839CrossRefPubMed Kim TW, Choi HJ, Kim NJ, Kim DH (2009) Anxiolytic-like effects of ginsenosides Rg3 and Rh2 from red ginseng in the elevated plus-maze model. Planta Med 75:836–839CrossRefPubMed
24.
Zurück zum Zitat Ahn EJ, Choi GJ, Kang H, Baek CW, Jung YH, Woo YC et al (2016) Antinociceptive effects of ginsenoside Rg3 in a rat model of incisional pain. European surgical research. Eur Surg Res 57:211–223CrossRefPubMed Ahn EJ, Choi GJ, Kang H, Baek CW, Jung YH, Woo YC et al (2016) Antinociceptive effects of ginsenoside Rg3 in a rat model of incisional pain. European surgical research. Eur Surg Res 57:211–223CrossRefPubMed
25.
Zurück zum Zitat Jiang B, Huang C, Chen XF, Tong LJ, Zhang W (2015) Tetramethylpyrazine produces antidepressant-like effects in mice through promotion of BDNF signaling pathway. Int J Neuropsychopharmcol 18 (pii:pw010) Jiang B, Huang C, Chen XF, Tong LJ, Zhang W (2015) Tetramethylpyrazine produces antidepressant-like effects in mice through promotion of BDNF signaling pathway. Int J Neuropsychopharmcol 18 (pii:pw010)
26.
Zurück zum Zitat Jiang B, Huang C, Zhu Q, Tong LJ, Zhang W (2015) WY14643 produces anti-depressant-like effects in mice via the BDNF signaling pathway. Psychopharmacology 232:1629–1642CrossRefPubMed Jiang B, Huang C, Zhu Q, Tong LJ, Zhang W (2015) WY14643 produces anti-depressant-like effects in mice via the BDNF signaling pathway. Psychopharmacology 232:1629–1642CrossRefPubMed
27.
Zurück zum Zitat He B, Chen P, Yang J, Yun Y, Zhang X, Yang R et al (2012) Neuroprotective effect of 20(R)-ginsenoside Rg(3) against transient focal cerebral ischemia in rats. Neurosci Lett 526:106–111CrossRefPubMed He B, Chen P, Yang J, Yun Y, Zhang X, Yang R et al (2012) Neuroprotective effect of 20(R)-ginsenoside Rg(3) against transient focal cerebral ischemia in rats. Neurosci Lett 526:106–111CrossRefPubMed
28.
Zurück zum Zitat Braun A, Lommatzsch M, Neuhaus-Steinmetz U, Quarcoo D, Glaab T, McGregor GP et al (2004) Brain-derived neurotrophic factor (BDNF) contributes to neuronal dysfunction in a model of allergic airway inflammation. Br J Pharmacol 141:431–440CrossRefPubMedPubMedCentral Braun A, Lommatzsch M, Neuhaus-Steinmetz U, Quarcoo D, Glaab T, McGregor GP et al (2004) Brain-derived neurotrophic factor (BDNF) contributes to neuronal dysfunction in a model of allergic airway inflammation. Br J Pharmacol 141:431–440CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Chen J, Zhang C, Jiang H, Li Y, Zhang L, Robin A et al (2005) Atorvastatin induction of VEGF and BDNF promotes brain plasticity after stroke in mice. J Cereb Blood Flow Metab 25:281–290CrossRefPubMedPubMedCentral Chen J, Zhang C, Jiang H, Li Y, Zhang L, Robin A et al (2005) Atorvastatin induction of VEGF and BDNF promotes brain plasticity after stroke in mice. J Cereb Blood Flow Metab 25:281–290CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Zhu XH, Yan HC, Zhang J, Qu HD, Qiu XS, Chen L et al (2010) Intermittent hypoxia promotes hippocampal neurogenesis and produces antidepressant-like effects in adult rats. J Neurosci 30:12653–12663CrossRefPubMed Zhu XH, Yan HC, Zhang J, Qu HD, Qiu XS, Chen L et al (2010) Intermittent hypoxia promotes hippocampal neurogenesis and produces antidepressant-like effects in adult rats. J Neurosci 30:12653–12663CrossRefPubMed
31.
Zurück zum Zitat Shichinohe H, Ishihara T, Takahashi K, Tanaka Y, Miyamoto M, Yamauchi T et al (2015) Bone marrow stromal cells rescue ischemic brain by trophic effects and phenotypic change toward neural cells. Neurorehabil Neural Repair 29:80–89CrossRefPubMed Shichinohe H, Ishihara T, Takahashi K, Tanaka Y, Miyamoto M, Yamauchi T et al (2015) Bone marrow stromal cells rescue ischemic brain by trophic effects and phenotypic change toward neural cells. Neurorehabil Neural Repair 29:80–89CrossRefPubMed
32.
Zurück zum Zitat Kleinridders A, Schenten D, Könner AC, Belgardt BF, Mauer J, Okamura T et al (2009) MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity. Cell Metab 10:249–259CrossRefPubMedPubMedCentral Kleinridders A, Schenten D, Könner AC, Belgardt BF, Mauer J, Okamura T et al (2009) MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity. Cell Metab 10:249–259CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Porsolt RD, Bertin A, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336PubMed Porsolt RD, Bertin A, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336PubMed
34.
Zurück zum Zitat Jiang B, Wang F, Yang S, Fang P, Deng ZF, Xiao JL et al (2015) SKF83959 produces antidepressant effects in a chronic social defeat stress model of depression through BDNF-TrkB pathway. Int J Neuropsychopharmacol 18 (pii:pyu096) Jiang B, Wang F, Yang S, Fang P, Deng ZF, Xiao JL et al (2015) SKF83959 produces antidepressant effects in a chronic social defeat stress model of depression through BDNF-TrkB pathway. Int J Neuropsychopharmacol 18 (pii:pyu096)
35.
Zurück zum Zitat Jiang B, Song L, Wang CN, Zhang W, Huang C, Tong LJ (2016) Antidepressant-Like Effects of GM1 Ganglioside Involving the BDNF Signaling Cascade in Mice. Int J Neuropsychopharmacol 19 (pii:pyw046) Jiang B, Song L, Wang CN, Zhang W, Huang C, Tong LJ (2016) Antidepressant-Like Effects of GM1 Ganglioside Involving the BDNF Signaling Cascade in Mice. Int J Neuropsychopharmacol 19 (pii:pyw046)
36.
Zurück zum Zitat Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85:367–370CrossRefPubMed Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85:367–370CrossRefPubMed
37.
Zurück zum Zitat Sarkisyan G, Roberts AJ, Hedlund PB (2010) The 5-HT(7) receptor as a mediator and modulator of antidepressant-like behavior. Behav Brain Res 209:99–108CrossRefPubMedPubMedCentral Sarkisyan G, Roberts AJ, Hedlund PB (2010) The 5-HT(7) receptor as a mediator and modulator of antidepressant-like behavior. Behav Brain Res 209:99–108CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Jiang B, Wang W, Wang F, Hu ZL, Xiao JL, Yang S et al (2013) The stability of NR2B in the nucleus accumbens controls behavioral and synaptic adaptations to chronic stress. Biol Psychiatry 74:145–155CrossRefPubMed Jiang B, Wang W, Wang F, Hu ZL, Xiao JL, Yang S et al (2013) The stability of NR2B in the nucleus accumbens controls behavioral and synaptic adaptations to chronic stress. Biol Psychiatry 74:145–155CrossRefPubMed
39.
Zurück zum Zitat Yao W, Gu C, Shao H, Meng G, Wang H, Jing X et al (2015) Tetrahydroxystilbene glucoside improves TNF-alpha-induced endothelial dysfunction: involvement of TGFbeta/Smad pathway and inhibition of vimentin expression. Am J Chin Med 43:183–198CrossRefPubMed Yao W, Gu C, Shao H, Meng G, Wang H, Jing X et al (2015) Tetrahydroxystilbene glucoside improves TNF-alpha-induced endothelial dysfunction: involvement of TGFbeta/Smad pathway and inhibition of vimentin expression. Am J Chin Med 43:183–198CrossRefPubMed
40.
Zurück zum Zitat Meng G, Yang S, Chen Y, Yao W, Zhu H, Zhang W (2015) Attenuating effects of dihydromyricetin on angiotensin II-induced rat cardiomyocyte hypertrophy related to antioxidative activity in a NO-dependent manner. Pharm Biol 53:904–912CrossRefPubMed Meng G, Yang S, Chen Y, Yao W, Zhu H, Zhang W (2015) Attenuating effects of dihydromyricetin on angiotensin II-induced rat cardiomyocyte hypertrophy related to antioxidative activity in a NO-dependent manner. Pharm Biol 53:904–912CrossRefPubMed
41.
Zurück zum Zitat Xu X, He M, Liu T, Zeng Y, Zhang W (2015) Effect of salusin-beta on peroxisome proliferator-activated receptor gamma gene expression in vascular smooth muscle cells and its possible mechanism. Cell Physiol Biochem 36:2466–2479CrossRefPubMed Xu X, He M, Liu T, Zeng Y, Zhang W (2015) Effect of salusin-beta on peroxisome proliferator-activated receptor gamma gene expression in vascular smooth muscle cells and its possible mechanism. Cell Physiol Biochem 36:2466–2479CrossRefPubMed
42.
Zurück zum Zitat Cryan JF, Holmes A (2005) The ascent of mouse: advances in modelling human depression and anxiety. Nat Rev Drug Discov 4:775–790CrossRefPubMed Cryan JF, Holmes A (2005) The ascent of mouse: advances in modelling human depression and anxiety. Nat Rev Drug Discov 4:775–790CrossRefPubMed
43.
Zurück zum Zitat Cryan JF, Slattery DA (2007) Animal models of mood disorders: recent developments. Curr Opin Psychiatry 20:1–7CrossRefPubMed Cryan JF, Slattery DA (2007) Animal models of mood disorders: recent developments. Curr Opin Psychiatry 20:1–7CrossRefPubMed
44.
Zurück zum Zitat Bourin M, Fiocco AJ, Clenet F (2001) How valuable are animal models in defining antidepressant activity? Hum Psychopharmacol 16:9–21CrossRefPubMed Bourin M, Fiocco AJ, Clenet F (2001) How valuable are animal models in defining antidepressant activity? Hum Psychopharmacol 16:9–21CrossRefPubMed
45.
Zurück zum Zitat Berton O, McClung CA, Dileone RJ, Krishnan V, Renthal W, Russo SJ et al (2006) Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 311:864–868CrossRefPubMed Berton O, McClung CA, Dileone RJ, Krishnan V, Renthal W, Russo SJ et al (2006) Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 311:864–868CrossRefPubMed
46.
Zurück zum Zitat Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ (2006) Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci 9:519–525CrossRefPubMed Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ (2006) Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci 9:519–525CrossRefPubMed
47.
Zurück zum Zitat Barth M, Kriston L, Klostermann S, Barbui C, Cipriani A, Linde K (2016) Efficacy of selective serotonin reuptake inhibitors and adverse events: meta-regression and mediation analysis of placebo-controlled trials. Br J Psychiatry 208:114–119CrossRefPubMed Barth M, Kriston L, Klostermann S, Barbui C, Cipriani A, Linde K (2016) Efficacy of selective serotonin reuptake inhibitors and adverse events: meta-regression and mediation analysis of placebo-controlled trials. Br J Psychiatry 208:114–119CrossRefPubMed
48.
Zurück zum Zitat Coryell MW, Wunsch AM, Haenfler JM, Allen JE, Schnizler M, Ziemann AE et al (2009) Acid-sensing ion channel-1a in the amygdala, a novel therapeutic target in depression-related behavior. J Neurosci 29:5381–5388CrossRefPubMedPubMedCentral Coryell MW, Wunsch AM, Haenfler JM, Allen JE, Schnizler M, Ziemann AE et al (2009) Acid-sensing ion channel-1a in the amygdala, a novel therapeutic target in depression-related behavior. J Neurosci 29:5381–5388CrossRefPubMedPubMedCentral
49.
Zurück zum Zitat Duman RS, Heninger GR, Nestler EJ (1997) A molecular and cellular theory of depression. Arch Gen Psychiatry 54:597–606CrossRefPubMed Duman RS, Heninger GR, Nestler EJ (1997) A molecular and cellular theory of depression. Arch Gen Psychiatry 54:597–606CrossRefPubMed
51.
Zurück zum Zitat Castren E, Rantamaki T (2008) Neurotrophins in depression and antidepressant effects. Novartis Found Symp 289:43–52 discussion 53-49, 87-93 CrossRefPubMed Castren E, Rantamaki T (2008) Neurotrophins in depression and antidepressant effects. Novartis Found Symp 289:43–52 discussion 53-49, 87-93 CrossRefPubMed
52.
Zurück zum Zitat Lee S, Lee MS, Kim CT, Kim IH, Kim Y (2012) Ginsenoside Rg3 reduces lipid accumulation with AMP-activated protein kinase (AMPK) activation in HepG2 cells. Int J Mol Sci 13:5729–5739CrossRefPubMedPubMedCentral Lee S, Lee MS, Kim CT, Kim IH, Kim Y (2012) Ginsenoside Rg3 reduces lipid accumulation with AMP-activated protein kinase (AMPK) activation in HepG2 cells. Int J Mol Sci 13:5729–5739CrossRefPubMedPubMedCentral
53.
Zurück zum Zitat Hien TT, Kim ND, Pokharel YR, Oh SJ, Lee MY, Kang KW (2010) Ginsenoside Rg3 increases nitric oxide production via increases in phosphorylation and expression of endothelial nitric oxide synthase: essential roles of estrogen receptor-dependent PI3-kinase and AMP-activated protein kinase. Toxicol Appl Pharmacol 246:171–183CrossRefPubMed Hien TT, Kim ND, Pokharel YR, Oh SJ, Lee MY, Kang KW (2010) Ginsenoside Rg3 increases nitric oxide production via increases in phosphorylation and expression of endothelial nitric oxide synthase: essential roles of estrogen receptor-dependent PI3-kinase and AMP-activated protein kinase. Toxicol Appl Pharmacol 246:171–183CrossRefPubMed
54.
Zurück zum Zitat Hwang JT, Lee MS, Kim HJ, Sung MJ, Kim HY, Kim MS et al (2009) Antiobesity effect of ginsenoside Rg3 involves the AMPK and PPAR-gamma signal pathways. Phytother Res 23:262–266CrossRefPubMed Hwang JT, Lee MS, Kim HJ, Sung MJ, Kim HY, Kim MS et al (2009) Antiobesity effect of ginsenoside Rg3 involves the AMPK and PPAR-gamma signal pathways. Phytother Res 23:262–266CrossRefPubMed
55.
Zurück zum Zitat Park MW, Ha J, Chung SH (2008) 20(S)-ginsenoside Rg3 enhances glucose-stimulated insulin secretion and activates AMPK. Biol Pharm Bull 31:748–751CrossRefPubMed Park MW, Ha J, Chung SH (2008) 20(S)-ginsenoside Rg3 enhances glucose-stimulated insulin secretion and activates AMPK. Biol Pharm Bull 31:748–751CrossRefPubMed
56.
Zurück zum Zitat Kim DM, Leem YH (2016) Chronic stress-induced memory deficits are reversed by regular exercise via AMPK-mediated BDNF induction. Neuroscience 324:271–285CrossRefPubMed Kim DM, Leem YH (2016) Chronic stress-induced memory deficits are reversed by regular exercise via AMPK-mediated BDNF induction. Neuroscience 324:271–285CrossRefPubMed
57.
Zurück zum Zitat Ghadernezhad N, Khalaj L, Pazoki-Toroudi H, Mirmasoumi M, Ashabi G (2016) Metformin pretreatment enhanced learning and memory in cerebral forebrain ischaemia: the role of the AMPK/BDNF/P70SK signalling pathway. Pharm Biol 54:2211–2219CrossRefPubMed Ghadernezhad N, Khalaj L, Pazoki-Toroudi H, Mirmasoumi M, Ashabi G (2016) Metformin pretreatment enhanced learning and memory in cerebral forebrain ischaemia: the role of the AMPK/BDNF/P70SK signalling pathway. Pharm Biol 54:2211–2219CrossRefPubMed
58.
Zurück zum Zitat Yoon H, Oh YT, Lee JY, Choi JH, Lee JH, Baik HH et al (2008) Activation of AMP-activated protein kinase by kainic acid mediates brain-derived neurotrophic factor expression through a NF-kappaB dependent mechanism in C6 glioma cells. Biochem Biophys Res Commun 371:495–500CrossRefPubMed Yoon H, Oh YT, Lee JY, Choi JH, Lee JH, Baik HH et al (2008) Activation of AMP-activated protein kinase by kainic acid mediates brain-derived neurotrophic factor expression through a NF-kappaB dependent mechanism in C6 glioma cells. Biochem Biophys Res Commun 371:495–500CrossRefPubMed
59.
Zurück zum Zitat Lee B, Sur B, Park J, Kim SH, Kwon S, Yeom M et al (2013) Ginsenoside rg3 alleviates lipopolysaccharide-induced learning and memory impairments by anti-inflammatory activity in rats. Biomol Ther (Seoul) 21:381–390CrossRef Lee B, Sur B, Park J, Kim SH, Kwon S, Yeom M et al (2013) Ginsenoside rg3 alleviates lipopolysaccharide-induced learning and memory impairments by anti-inflammatory activity in rats. Biomol Ther (Seoul) 21:381–390CrossRef
60.
Zurück zum Zitat Chen SD, Wang YL, Liang SF, Shaw FZ (2016) Rapid amygdala kindling causes motor seizure and comorbidity of anxiety- and depression-like behaviors in rats. Front Behav Neurosci 10:129PubMedPubMedCentral Chen SD, Wang YL, Liang SF, Shaw FZ (2016) Rapid amygdala kindling causes motor seizure and comorbidity of anxiety- and depression-like behaviors in rats. Front Behav Neurosci 10:129PubMedPubMedCentral
61.
Zurück zum Zitat Wang J, Jiang C, Chen L, Wu S, Lin J, Gao L et al (2016) A cross-sectional study to investigate the correlation between depression comorbid with anxiety and serum lipid levels. Compr Psychiatry 69:163–168CrossRefPubMed Wang J, Jiang C, Chen L, Wu S, Lin J, Gao L et al (2016) A cross-sectional study to investigate the correlation between depression comorbid with anxiety and serum lipid levels. Compr Psychiatry 69:163–168CrossRefPubMed
62.
Zurück zum Zitat Wu S, Gao Q, Zhao P, Gao Y, Xi Y, Wang X et al (2016) Sulforaphane produces antidepressant- and anxiolytic-like effects in adult mice. Behav Brain Res 301:55–62CrossRefPubMed Wu S, Gao Q, Zhao P, Gao Y, Xi Y, Wang X et al (2016) Sulforaphane produces antidepressant- and anxiolytic-like effects in adult mice. Behav Brain Res 301:55–62CrossRefPubMed
63.
Zurück zum Zitat Caccamo A, Maldonado MA, Bokov AF, Majumder S, Oddo S (2010) CBP gene transfer increases BDNF levels and ameliorates learning and memory deficits in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA 107:22687–22692CrossRefPubMedPubMedCentral Caccamo A, Maldonado MA, Bokov AF, Majumder S, Oddo S (2010) CBP gene transfer increases BDNF levels and ameliorates learning and memory deficits in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA 107:22687–22692CrossRefPubMedPubMedCentral
64.
Zurück zum Zitat Karamohamed S, Latourelle JC, Racette BA, Perlmutter JS, Wooten GF, Lew M et al (2005) BDNF genetic variants are associated with onset age of familial Parkinson disease: GenePD Study. Neurology 65:1823–1825CrossRefPubMed Karamohamed S, Latourelle JC, Racette BA, Perlmutter JS, Wooten GF, Lew M et al (2005) BDNF genetic variants are associated with onset age of familial Parkinson disease: GenePD Study. Neurology 65:1823–1825CrossRefPubMed
Metadaten
Titel
Antidepressant-like effects of ginsenoside Rg3 in mice via activation of the hippocampal BDNF signaling cascade
verfasst von
Zhengchen You
Qi Yao
Jianhong Shen
Zhikai Gu
Hui Xu
Zhonghua Wu
Chuanjun Chen
Luozhu Li
Publikationsdatum
24.12.2016
Verlag
Springer Japan
Erschienen in
Journal of Natural Medicines / Ausgabe 2/2017
Print ISSN: 1340-3443
Elektronische ISSN: 1861-0293
DOI
https://doi.org/10.1007/s11418-016-1066-1

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